1. Field of the Invention
The present invention relates to a sonodynamic treatment apparatus for sonodynamic treatment using an ultrasound and a method of controlling monitoring the same, and particularly to a sonodynamic treatment apparatus for performing the sonodynamic treatment using the ultrasound together with a medicine for the sonodynamic treatment activated by cavitation generated by the ultrasound radiation and a method of monitoring the same.
2. Description of the Related Art
Ultrasound scanners are widely used as apparatuses utilizing ultrasounds in a medical technical field. The ultrasound scanners are superior in real time among various types of diagnostic imaging apparatuses currently in use and have advantageous effects such as low costs and small sizes.
Further, the ultrasound is utilized in treatment for cancer in addition to diagnosis. As a medical treatment method using the ultrasound, is disclosed High Intensity Focused Ultrasound (HIFU) of a thermal coagulation treatment in which a tissue is coagulated to go necrosis by energy of the ultrasound which is absorbed by the tissue and converted into heat (see, for example, P. P. Lele, “Ultrasound; medical applications, biological effects and hazard potential”, Plenum Press New York 1987:275-306.) Such the thermal coagulation treatment begins to be actually used for patients of benign prostatic hyperplasia, prostatic cancer, breast cancer, and the like.
As described above, the ultrasound, capable of being used both for the diagnosis and the treatment, provides an integration system which is efficient and effective for treating patients (see, for example, WO96/506636.)
However, the thermal coagulation treatment, radiating a focused ultrasound having an acoustic intensity more than 1 kW/cm2 toward an affected part, has a possibility of an increased risk of a patient if an aiming point is off an affected part. Further, the thermal coagulation treatment is considered to be unsuitable for treating invasive and disseminated cancer in which normal tissues and cancer tissues are complicated.
On the other hand, a sonodynamic treatment using an ultrasound having a low acoustic intensity from several watts/cm2 to several tens watts/cm2 is disclosed (see, for example, Yumita et al., March 1989, Jpn. J. Cancer Res., 80: 219-222.) The sonodynamic treatment is a method for treating a patient by activating a medicine for the sonodynamic treatment previously administered in the patient using a phenomenon called cavitation generated by ultrasound insonation.
The cavitation is a sequential phenomenon in which a bubble is generated by the ultrasound insonation, the generated bubble grows gradually, and the grown bubble collapses suddenly. The collapse of the bubble at a last process of the cavitation generates an extremely high pressure (hundreds of atmospheric pressures) and an extremely high temperature (thousands degrees) in very short time with formation of a unique reaction field around the bubble.
Among medicines for the sonodynamic treatment, is disclosed a medicine accumulating in a tumor to decrease a threshold for a level of ultrasound necessary for the cavitation, such as rose bengal derivative, upon being located in the reaction field generated by the cavitation, showing an antitumor effect (see, for example, a pamphlet of WO98/01131.)
As mentioned above, the sonodynamic treatment is expected to have a high selectivity because the affected part is double targeted with the medicine and the ultrasound.
Further, for the sonodynamic treatment, are disclosed methods of radiating an ultrasound having a lower acoustic intensity enough to cause the cavitation than conventional one. For example, Japanese laid open patent application publication No. 2-126848 discloses a method of radiating the ultrasound in which acoustic fields are switched. A pamphlet of WO94/06380 discloses a method of superimposing a second harmonic on the fundamental. It is also disclosed that a method of periodic shifting of second-harmonic phase on the fundamental (see, for example, Kawabata et al., (2003) Jpn. J. Appl. Phys., 42: 3246-3250.)
Both methods efficiently grow the cavitation by promoting growth of the bubble generated by ultrasound exposure up to a size resonant with the frequency of the radiated ultrasound.
In addition, for example, it is disclosed that the growth of the bubble once generated requires to be successively exposed to three or more pulses of the ultrasound (see, for example, Xu et al. (2003) IEEE Ultrasonics Symposium Proc., 1086-1089 and Xu et al. (2004) IEEE Trans. Ultrason., Ferroelect. Freq. Contr., 51: 726-736.)
A plurality of methods are disclosed for monitoring a treatment area during Lithotripsy and ultrasound thermal coagulation treatment. For example, Japanese Patent No. 2644217 discloses a method of confirming a position of a calculus using a weak ultrasound before treatment. Japanese Patent No. 3225526 discloses a method of confirming a position of a broken calculus and a position of collapsed cavitation by detecting positions of even-number-times harmonics on images of the ultrasound in a plurality of different directions. Japanese laid open patent application publication No. 2003-33365 discloses a method of confirming that a temperature reaches such a value as to surely cause thermal denaturation in a tissue by confirming generation of a bubble by detecting even-number-times harmonics.
Particularly, it is disclosed that a method of making observation possible under treatment at a treatment area by stopping radiation of the ultrasound for treatment only when an ultrasound for diagnosis is used for visualizing an area around the treatment area by synchronizing an ultrasound diagnosis apparatus with a thermal coagulation treating apparatus to overcome a difficulty in ultrasound diagnosis due to interference of the ultrasound for the thermal coagulation under radiation with ultrasound for diagnosis (see, for example, Vaezy et al. (2000) Ultraso. Med. Biol., 27: 33-42.)
Further, in the thermal coagulation treatment, are disclosed technologies in which operation of the ultrasound is made to acquire an ultrasound diagnosis image only while radiation of the ultrasound for treatment is stopped (see, for example, U.S. Pat. No. 6,095,980 and Japanese laid open patent application publication No. 2000-229098.)
As mentioned above, the sonodynamic treatment is expected as an effective treatment method for a tumor because it provides a little potential risk to a patient. Further, in the sonodynamic treatment, a method of the ultrasound exposure which efficiently causes a cavitation phenomenon as a source of treatment using an ultrasound of which acoustic intensity is relatively low in the sonodynamic treatment.